Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation†

Maternal use of antidepressants has increased throughout the last decades; selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressants. Despite the widespread use of SSRI by women during reproductive age and pregnant women, an increasing amount of research warns of possible detrimental effects of maternal use of SSRI during pregnancy including low birthweight/small for gestational age and preterm birth. In this review, we revisited the impact of maternal use of SSRI during pregnancy, its impact on serotonin homeostasis in the maternal and fetal circulation and the placenta, and its impact on pregnancy outcomes-particularly intrauterine growth restriction and preterm birth. Maternal use of SSRI increases maternal and fetal serotonin. The increase in maternal circulating serotonin and serotonin signaling likely promotes vasoconstriction of the uterine and placental vascular beds decreasing blood perfusion to the uterus and consequently to the placenta and fetus with potential impact on placental function and fetal development. Several adverse pregnancy outcomes are similar between women, sheep, and rodents (decreased placental size, decreased birthweight, shorter gestation length/preterm birth, neonatal morbidity, and mortality) highlighting the importance of animal studies to assess the impacts of SSRI. Herein, we address the complex interactions between maternal SSRI use during gestation, circulating serotonin, and the regulation of blood perfusion to the uterus and fetoplacental unit, fetal growth, and pregnancy complications.